Ok, to understand anything you need to understand all the terms, so, what does “attenuate” mean?, it simply means to make weaker or less effective

To be able to explain the above, all you need to do is understand the triple whammy effect

The term “triple whammy” refers to the risk of acute kidney injury when an ACEI or ARB is combined with a diuretic and NSAID. This combination might be seen in a patient with hypertension, congestive heart failure, or renal disease who has arthritis or other mild to moderate pain.

Mechanism

To understand how the triple whammy works, it is necessary to understand how each medication in the three drugs combination affects the kidney when given alone:

ACEIs or ARBs: To understand this, you need to understand the RAAS system,this system produces angiotensin II which functions to;

1. Cause vasoconstriction

2. Increase thirst by stimulating the thirst centre in the hypothalamus

3. Stimulate aldosterone release which in turn brings about salt and water retention.

NB; ACEIs/ARBs in Inhibits angiotensin II and hence bringing the above three functions to standstill.

NSAIDs: reduce blood flow to the glomerulus by inhibiting production of vasodilating prostaglandins.(recall the cyclooxygenase pathway).

When renal perfusion is impaired by a diuretic/dehydration, renin secretion and angiotensin II production is triggered. Angiotensin II then works to improve renal blood flow by vasoconstricting the efferent arteriole(artery that takes blood away from the kidney) to help maintain intraglomerular pressure.

Prostaglandin synthesis is another compensatory mechanism; prostaglandins dilate the afferent arteriole(artery that brings blood to the kidney) to increase blood flow to the glomerulus. But when the patient is also on an ACEI or ARB and an NSAID, these compensatory mechanisms are impaired and that is how Nonsteroidal anti-inflammatory drugs(NSAIDs) attenuate the diuretic response to loop diuretics in part by preventing prostaglandin-mediated increase in renal blood flow….. UNDERSTAND!!!